Human cytomegalovirus (HCMV) is a member of the medically significant Herpesviridae family of viruses, a family divided into three subfamilies: alpha-, beta- and gamma-herpesviruses. Herpesviruses establish a life-long relationship with their hosts and can manifest disease in an opportunistic manner. HCMV is the most common viral cause of congenital birth defects and is responsible for significant morbidity and mortality in immunocompromised patients, including AIDS patients and organ transplant recipients.1,2 A notable feature of HCMV pathogenesis is its exceptionally broad tissue tropism. HCMV is capable of manifesting disease in most organ systems and tissue types, which directly correlates with its ability to infect fibroblasts, endothelial cells, epithelial cells, monocytes/macrophages, smooth muscle cells, stromal cells, neuronal cells, neutrophils, and hepatocytes.3-5 In vitro entry into target cells is equally promiscuous, as HCMV is able to bind, penetrate and initiate replication in all tested vertebrate cell types.6 Recently, epidermal growth factor receptor (EGFR) was identified as a cellular receptor for HCMV. Expression of EGFR was found to correlate with the ability of the virus to initiate gene expression.7 However, EGFR is not expressed on several HCMV-permissive cells, such as hematopoetic cell types. Therefore other receptors that HCMV can exploit to gain entry into various cell types must exist.
Many of the physiological consequences associated with HCMV infection are consistent with activation of cellular integrins. Host cells respond to HCMV infection by activating numerous signal transduction pathways including initiating Ca++ influx at the cell membrane, as well as activating phospolipases C and A2, mitogen-activated protein kinase (MAP kinase), p38, NF-KB and SP-1.8,9 HCMV also induces a distinct cytopathology, with cells rounding 30-60 minutes post-viral challenge corresponding to the entry event and then once again 24 hours post-infection.10 
In recent years, cellular integrins have emerged as entry receptors for a broad range of pathogens including pathogenic plant spores, bacteria and several families of viruses. Integrins have been shown to mediate both the initial attachment of virions to the cell surface, as well as to facilitate the “post-attachment” or internalization entry step.11 Integrins are expressed on the cell surface as a noncovalently linked heterodimer consisting of a α and β subunit, which conveys specificity in cell-cell adhesion, cell-extracellular matrix (ECM) adhesion, immune cell recruitment, extravasation and signaling.12,13 Although each specific integrin heterodimer has a specific set of ligands, many integrin heterodimers have overlapping ligand-binding capabilities, a characteristic that many pathogens have evolved to exploit; most viruses that utilize integrins as receptors are capable of interacting with several integrin heterodimers.
There are several known integrin recognition motifs. The most common of these involves the amino acid sequence RGD. There are, however, a number of RGD-independent integrin recognition motifs. These include motifs found in certain extracellular matrix proteins and the disintegrin-like domain found in the family of proteins known as ADAMS (A Disintegrin And a Metalloprotease).14 From the 30 known members of the ADAM family, a disintegrin-like domain consensus and minimum integrin recognition motif has been identified (RX5-7DLXXF/L) (SEQ. ID. NOS: 23-28).14,15 
Researchers have established that viral glycoprotein B (gB) is a protein that is required for virus entry and fusion throughout the Herpesviridae family. Glycoprotein B is a critical member of the conserved basic fusion machinery.16 During virus entry, HCMV induces cellular morphological changes and signaling cascades consistent with engagement of cellular integrins; however, HCMV structural proteins do not possess the widely used RGD integrin binding motif. Thus, it would be desirable to identify a conserved receptor-binding domain within the Herpesviridae family that can be used to inhibit viral entry into host cells.